Isihloko
I-Methylene Blue Nokuphazamiseka Kwe-Bipolar: Ukuhlola Ucwaningo Lwezokwelapha
Inguqulo emfushane
I-methylene blue isihlolwe ekuphazamisekeni kwe-bipolar isikhathi eside kunalokho abantu abaningi abakucabangayo, kusukela ngawo-1970s lapho abacwaningi befuna ezinye izindlela nemithi yokwengeza ku-lithium. Ubufakazi obukhona buncane: uchungechunge olulodwa lwezigameko olungafihli ukwelashwa, izivivinyo ezimbili ezindala ezilawulwayo, kanye nocwaningo olulodwa lwesimanje olwabela ukwelashwa ngokungahleliwe futhi lushintshanise ukwelashwa kubahlanganyeli. Uphawu olufanayo kuzo zonke ukuthuthuka kwezimpawu zokucindezeleka nezisele lapho i-methylene blue yengezwa ekwelashweni okukhona. Alukho ucwaningo olwabonisa umphumela wokunciphisa i-mania, futhi alukho olwabonisa uphawu olucacile lokushintshela ku-mania, nakuba izinani zabahlanganyeli zazincane kakhulu ukuba zixazulule umbuzo walokho kushintsha. Noma ubani ohlola le nhlanganisela kufanele abheke lezi njengezifundo zokwelashwa okwengeziwe, hhayi ubufakazi bokuyisebenzisa yodwa, futhi acabangele izixwayiso zokusebenzisana kwemithi ngaphambi kokufinyelela eziphethweni ezingasetshenziswa.
Kungani ukuphazamiseka kwe-bipolar kwadonsa ukunaka kusenesikhathi
Isizathu sasingakaze sibe ukuthi i-methylene blue yayifana nomuthi ojwayelekile ozinzisa imizwa. Ngokwakheka ifana nama-phenothiazine, futhi abacwaningi bokuqala babecabanga ukuthi ingase iguqule i-vanadate ekuyi-plasma ibe yisimo esingasebenzi kakhulu, iguqule ukusebenza kwe-sodium-potassium ATPase okuhlotshaniswa nokushintshashintsha kwemizwa. Ukuze bahlole lo mbono, uNaylor nozakwabo belapha iziguli ezimbili ezazilokhu zishintshashintsha imizwa futhi babona izikhathi ezinde lapho imizwa izinzile, okwakhuthaza konke okwalandela. Ukulandisa kukaHowland ngomlando we-methylene blue kwezokwelapha kwengqondo kubeka lo msebenzi esimweni sawo, kulandelela le nhlanganisela kusukela ekubeni isandulela sama-phenothiazine kuya ekubeni into ehlolwayo ethinta ukusebenza kwengqondo.
Ucwaningo lwakamuva lwezindlela zokusebenza lwalushintsha lolu hlaka lwesizathu lwagxila ekusebenzeni kwe-mitochondria nasekulinganisweni kwe-redox. Ukungasebenzi kahle kwe-mitochondria kuhlotshaniswe nokuphazamiseka kwe-bipolar ngezifundo zemindeni, okutholakele ekubonakalisweni kwezakhi zofuzo ngemva kokufa, kanye nezibonelo zezilwane ezifana negundane elinoshintsho kufuzo lwe-POLG1, elinezici ezifana ne-bipolar ezisabela ngokwengxenye ku-lithium. Ukubuyekezwa kuka-Alda kwango-2019 kwe-methylene blue ekuphazamisekeni kwemizwa nengqondo kuphakamisa ukuthi ikhono lale nhlanganisela lokudlulisa ama-electron adlule ezindaweni ezivinjiwe ochungechungeni lokuthuthwa kwama-electron, kunciphise ukuphuma kwezinhlobo ze-oxygen ezisabela kalula, liyenza ibe wusizo ekuhloleni imibono ngokuguqulwa kokusebenza kwe-mitochondria. Okunye ukubuyekezwa kwe-methylene blue njengento engase ibe umuthi wokulwa nokucindezeleka kwengeza ukuvinjelwa kwe-MAO-A, ukuvinjelwa kwe-nitric oxide synthase ne-guanylate cyclase, kanye nemiphumela yokunciphisa ukuvuvukala encazelweni yezindlela zokusebenza. Nokho, izindlela zokusebenza ziyimibono. Umbuzo wezokwelapha uthi izivivinyo zalinganisa ini, futhi ngaphansi kwaziphi izimo.
Izivivinyo, ngasinye
Uchungechunge lwezigameko lukaNarsapur noNaylor: iziguli ezingasabeli kahle ekwelashweni, ukwelashwa okungafihliwe
Umbiko wokuqala wawuwuchungechunge olungenalo iqembu lokulawula lweziguli ezingama-24 ezazigula isikhathi eside noma kakhulu, ezanikwa i-methylene blue yokwengeza ekwelashweni ngo-200 noma 300 mg nsuku zonke ngezikhathi ezisukela ezinsukwini kuya ngaphezu konyaka. Eziyi-19 zazinesifo se-bipolar (i-mania nokucindezeleka), futhi eziyi-14 kulezo eziyi-19 zabhekwa njengezazithuthuke ngokuqinisekile, okuyisilinganiso sokusabela esingamaphesenti angu-74. Iziguli ezintathu ukuxilongwa kwazo nge-bipolar okwakubhekwa njengokungaqinisekile azisabelanga.
Lokhu kubheke njengesisekelo sokwakha imibono, hhayi njengedatha yokusebenza kokwelashwa. Kwakungekho ukwabiwa ngokungahleliwe, ukufihlwa kokwelashwa, noma isikali esimisiwe, futhi imithi eyayisetshenziswa kakade ayibikwanga ngokuphelele. Isibalo samaphesenti angu-74 esivela ochungechungeni olungafihli ukwelashwa ezigulini ezingasabeli kahle sibonisa ukwahlulela nokukhetha kombukeli ngendlela efanayo naleyo esibonisa ngayo ukusebenza komuthi.
UNaylor nabanye ngo-1986: ukuvimbela ngokushintshanisa ukwelashwa iminyaka emibili kanye ne-lithium
Lolu kwakuwucwaningo olwalunenhloso enkulu kunazo zonke ezifundweni zokuqala: isivivinyo seminyaka emibili esifihle ukwelashwa kubahlanganyeli nakubacwaningi, sabela ngokungahleliwe futhi sashintshanisa ukwelashwa, ezigulini ezingama-31 ezazinesifo se-bipolar. Umhlanganyeli ngamunye kwakufanele athole 300 mg nsuku zonke unyaka owodwa kanye no-15 mg nsuku zonke komunye unyaka, ngokulandelana okwakukhethwe ngokungahleliwe. Umthamo we-15 mg wawusetshenziswa ukuqhathanisa, ukhethwe ikakhulukazi ngoba ukushintsha kombala womchamo kwakwenza kungabi nokwenzeka ukufihla i-placebo engasebenzi ngempela. Okubalulekile, wonke umhlanganyeli waqhubeka ne-lithium sonke isikhathi, ngakho lokhu kwakuwukwelashwa okwengeziwe kokuvimbela kusukela ekuqaleni.
Abayi-17 kwabangu-31 baqeda yomibili iminyaka. Kulabo abaqeda, izimpawu zokucindezeleka zazibuthakathaka kakhulu ngokwezibalo ngonyaka we-300 mg kunangonyaka we-15 mg, kuyilapho ukuqina kwezimpawu ze-mania kungahlukanga phakathi kwemithamo. Kwabikwa ukuthi amazinga okulaliswa esibhedlela ayephansi ngesikhathi sesivivinyo kunangaphambi kwaso, nakuba ukubuyekezwa kuka-Alda kwakamuva kuphawula ukuthi lokhu kwenzeka ngisho nangezikhathi ze-15 mg, okwenza ukuhumusha kube nzima. Abacwaningi ngokwabo baveza ubuthakathaka: isampula elincane, ukushiya ucwaningo kwamaphesenti angu-45, izikali zokulinganisa ezilula, ukufihlwa kokwelashwa okungabazekayo, kanye nokungaqiniseki ngokuthi i-15 mg yayingasebenzi yini ngokwemithi. Lokho kukhathazeka kokugcina kwabonakala kunesisekelo, njengoba kuchazwe ngezansi.
Ucwaningo lukaNaylor lokucindezeleka ngomthamo ophansi: kungani i-"placebo" kungenzeka yayisebenza
Ukuqhathanisa okwalandela okwathatha amasonto amathathu futhi kwafihla ukwelashwa kuzo zombili izinhlangothi kwahlola 15 mg nsuku zonke kuqhathaniswa ne-placebo engasebenzi ezigulini ezingama-35 ezinokucindezeleka okukhulu, kwathola ukuthi i-methylene blue yayiyidlula ngokubalulekile ngokwezibalo. Leli kwakuyiqembu lokucindezeleka elaligcwele kakhulu uhlobo lwe-unipolar kunokuba kube isivivinyo se-bipolar, ngakho liyingxenye yobufakazi obujwayelekile bokucindezeleka kunokuba libe sohlangothini lwe-bipolar. Ukubaluleka kwalo kubafundi abathanda i-bipolar kusezindleleni zocwaningo: umthamo we-15 mg owawusetshenziswa ukuqhathanisa kuzo zombili izivivinyo zokushintshanisa ukwelashwa wawusuyidlulile i-placebo engasebenzi. Ngakho noma yimuphi umehluko wokwelashwa olinganiswa uma kuqhathaniswa ne-15 mg cishe unciphisa umehluko ophelele uma kuqhathaniswa nokunganikwa lutho, futhi kusho ukuthi asikho kulezi zivivinyo ezindala esasinengalo ye-placebo yangempela.
U-Alda nabanye ngo-2017: isivivinyo sesimanje sokwelashwa okwengeziwe ngokushintshanisa
Ucwaningo oluqine kakhulu kuze kube manje lwabela ngokungahleliwe abantu abadala abangama-37 abanokuphazamiseka kwe-bipolar I noma II nezimpawu ezisele ukuba bathole i-methylene blue 195 mg nsuku zonke kuqhathaniswa no-15 mg nsuku zonke, ngamunye amasonto angu-13 ngokushintshanisa. Lokhu kwakuwukwelashwa okwengeziwe ngokusobala: wonke umhlanganyeli wayesezinzile esebenzisa i-lamotrigine okungenani izinyanga ezintathu futhi waqhubeka nayo, kuvunyelwe i-lithium, i-divalproex, imithi yokulwa ne-psychosis, kanye nemithi yokulwa nokucindezeleka ngemithamo engaguquki. Isivivinyo sifakwe ohlwini ku-PubMed 27284082. Izimpawu ekuqaleni zazisukela kwezithambile kuya kwezimaphakathi, ngesilinganiso samaphuzu okucindezeleka e-Hamilton esicishe sibe ngu-7.6 kanye namaphuzu e-Montgomery-Asberg acishe abe ngu-12.7.
Imiphumela yavuna i-195 mg ezilinganisweni zokucindezeleka nokukhathazeka. Kulabo abaqeda, ubukhulu bomphumela babucishe bube ngu-0.71 esikalini sokucindezeleka se-Hamilton, 0.80 esikalini se-Montgomery-Asberg, kanye no-0.79 esikalini sokukhathazeka se-Hamilton, ngakunye kubalulekile ngokwezibalo, futhi ukuhlaziywa okusebenzisa ukubonwa kokugcina njengokulinganisa okulandelayo kuzo zonke iziguli ezingama-37 kwanikeza imiphumela efanayo ebalulekile. Amaphuzu e-mania ahlala ephansi futhi ezinzile ngaphandle komphumela wokwelashwa, futhi iqoqo lezivivinyo zamakhono okuqonda alibonisanga inzuzo ebalulekile ezilinganisweni zenkumbulo yamazwi, ikhono lokuhlela nokulawula izenzo, noma ukunaka. Abahlanganyeli abayishumi baphuma ngenxa yezizathu ezihlanganisa ukubhebhetheka kwezimpawu ze-bipolar, ukukhathazeka, ukugcinwa koketshezi emzimbeni, kanye nokuhoxisa imvume. Imiphumela engathandeki ikakhulukazi kwakuwukushisa kwesikhashana lapho kuchanywa, ukuphazamiseka kwesisu namathumbu, kanye nekhanda elibuhlungu.
Ithebula lezivivinyo zokwelapha: okwahlolwa ngempela
| Ucwaningo | Ukwakheka kanye no-n | Umthamo we-methylene blue | Ukwelashwa okuhambisana nayo | Izilinganiso zomphumela | Umphumela oyinhloko | Imikhawulo |
|---|---|---|---|---|---|---|
| UNarsapur noNaylor, uchungechunge olungafihliwe | Uchungechunge lwezigameko olungalawulwayo, 24 sekukonke (19 abane-bipolar) | 200 kuya ku-300 mg nsuku zonke, izinsuku ezi-3 kuya ezinyangeni eziyi-19 | Iziguli ezingasabeli kahle ekwelashweni; izinhlelo zokwelashwa ezikhona azibikwanga ngokuphelele | Ukwahlulela kukadokotela ngokuthuthuka | Iziguli eziyi-14 kwezingu-19 ezine-bipolar zabhekwa njengezithuthukile | Alikho iqembu lokulawula, akukho ukufihlwa kokwelashwa, isilinganiso somphumela esincike ekwahluleleni, ukuchayeka okungafani |
| UNaylor nabanye ngo-1986 | Ukushintshanisa kokwelashwa okufihlwe kuzo zombili izinhlangothi iminyaka emi-2, 31 bangena, 17 baqeda | 300 mg kuqhathaniswa no-15 mg, unyaka owodwa ngamunye | I-lithium yaqhubeka kubo bonke abahlanganyeli | Izilinganiso zezimpawu zokucindezeleka ne-mania, ukulaliswa esibhedlela | Ukucindezeleka okungaqinile kangako ku-300 mg; akukho mehluko ku-mania | Ukushiya ucwaningo kwamaphesenti angu-45, izikali ezilula, ukufihlwa kokwelashwa okuphazamisekile, i-15 mg kungenzeka yayisebenza |
| Ucwaningo lukaNaylor lomthamo ophansi | I-RCT yamasonto ama-3 efihlwe kuzo zombili izinhlangothi kuqhathaniswa ne-placebo engasebenzi, n=35, ukucindezeleka okukhulu | 15 mg nsuku zonke | Imithi esetshenziswa kakade ayibikwanga ngokwanele | Ukuqina kokucindezeleka | I-15 mg yayidlula i-placebo | Akulona iqembu le-bipolar; abukho ubukhulu bomphumela obunezinombolo esifinyezweni esifakwe ohlwini |
| U-Alda nabanye ngo-2017 | Ukushintshanisa kokwelashwa okufihlwe kuzo zombili izinhlangothi amasonto ayi-13, 37 babelwa ngokungahleliwe, 27 baqeda | 195 mg kuqhathaniswa no-15 mg | I-lamotrigine kubo bonke; i-lithium, i-divalproex, imithi yokulwa ne-psychosis neyokulwa nokucindezeleka ivunyelwe uma ingaguquki | MADRS, HAM-D, HAM-A, YMRS, CGI-BP, amakhono okuqonda | Ukuthuthuka okubalulekile kokucindezeleka nokukhathazeka ku-195 mg; akukho mphumela ku-mania noma emakhonweni okuqonda | Isampula elincane, izimpawu ezisele (hhayi ezesigaba esibukhali), ukusebenzisa imithi eminingi, imiphumela eqhubeka isuka esigabeni esandulele, i-15 mg kungenzeka yayisebenza |
| Isivivinyo sikaNaylor se-mania | Ucwaningo lwe-mania olufihlwe kuzo zombili izinhlangothi, n=18 | Imininingwane ayiqinisekiseki embikweni ofakwe ohlwini | Akutholakali embikweni ofinyelelekayo | Izimpawu ze-mania | Ayikho inzuzo ebonisiwe yokunciphisa i-mania | Umbiko wamakhasi amabili, asikho isifinyezo esifakwe ohlwini, umthamo nesikali akuqinisekiseki |
Ukuhumusha iphethini ngokwethembeka
Kunezinto ezintathu ezibonwayo ezisasekelwa ngisho nalapho kucatshangelwa imikhawulo. Okokuqala, umphumela ukhomba ohlangothini olufanayo: izimpawu zokucindezeleka nezisele zathuthuka ngomthamo ophezulu kuzo zombili izifundo ezilawulwayo ze-bipolar, ngobukhulu bomphumela obumaphakathi esivivinyweni sesimanje. Okwesibili, akukho kulolu cwaningo okusekela isimangalo sokunciphisa i-mania. Isivivinyo esasiqondene ne-mania asitholanga inzuzo, futhi izifundo zokushintshanisa ukwelashwa azitholanga mehluko ku-mania, okuwukungabikho kokusebenza kokunciphisa i-mania, hhayi ubufakazi bokuzinzisa imizwa kuzo zombili izinhlangothi. Okwesithathu, alukho uphawu lwe-mania oluvela ngesikhathi sokwelashwa olwabonakala, kodwa leso sitatimende sinesisindo esincane. Amaphuzu e-mania ekuqaleni ayeseduze noziro futhi amasampula athola umuthi ayebalwa ngamashumi, ngakho lezi zifundo zazingeke zikwazi ukubona ingozi yokushintsha enobukhulu obubalulekile kwezokwelapha. Indlela efanele yokukusho ukuthi alukho uphawu lokushintsha olwabonwa, hhayi ukuthi ingozi yokushintsha yakhishwa njengengenzeka.
Izinkinga ezimbili zezindlela zocwaningo zidinga ukugcizelelwa ngoba zithinta bonke ubufakazi obukhona. Ukufihlwa kokwelashwa kwakuphazamisekile ngokwesakhiwo kuzo zonke izifundo zokushintshanisa ukwelashwa, ngoba i-methylene blue ishintsha umbala womchamo futhi umthamo ophansi wokuqhathanisa wakhethwa ngokuqondile ukuze ulingise lowo mphumela kuyilapho kucatshangwa ukuthi awusebenzi. Futhi lowo mcabango awuzange ume: umthamo ophansi wayidlula i-placebo engasebenzi ekucindezelekeni, okusho ukuthi ukuqhathanisa okubalulekile kwakuwukuqhathanisa imithamo phakathi kwezinhlelo ezimbili ezingase zombili zisebenze, kunokuba kube ukuhlola umuthi kuqhathaniswa ne-placebo. Ubukhulu bemiphumela obulinganiswa ngale ndlela kunzima ukubuhumusha futhi abunakuhlanganiswa nezivivinyo ezijwayelekile zemithi yokulwa nokucindezeleka ezilawulwa nge-placebo.
Ukugcina ucwaningo emkhakheni walo kubalulekile lapha. Lezi yizivivinyo ze-bipolar ezinezilinganiso zemiphumela eziqondene ne-bipolar, futhi akufanele zixutshwe nobufakazi obuvela kwamanye amaqembu abantu. Abafundi abathanda ucwaningo lwemikhakha esondelene nalona kufanele babheke okutholakele ngokukhathazeka, ucwaningo lwamakhono okuqonda, kanye nephrofayela yokuphepha nokusebenzisana kwemithi ngokwehlukana, ngoba ngakunye kunezindlela ezihlukile zokwakha ucwaningo nezinto okufanele zicatshangelwe ngengozi.
Umongo wokuphepha ekusetshenzisweni kwemithi eminingi ye-bipolar
Izixwayiso ezimbili zithinta ngokuqondile iziguli ze-bipolar, ezivame ukubhalelwa imithi ethinta i-serotonin. I-methylene blue kanye nomkhiqizo wayo wokugaywa emzimbeni, i-Azure B, ziyizivimbeli ezinamandla ze-MAO-A ezinokusebenza okubuyiseleka emuva, futhi ukuzinika kanye nama-SSRI, ama-SNRI, neminye imithi ethinta i-serotonin kungabangela i-serotonin syndrome. Cishe zonke izigameko zobuthi ezishicilelwe zazihilela i-methylene blue enikwa ngomthambo, futhi isivivinyo sesimanje se-bipolar savumela imithi yokulwa nokucindezeleka kubahlanganyeli abangama-20 kwabangu-37 ngaphandle kwesigameko esihlobene ne-serotonin, kodwa lokho okwenzeka eqenjini elincane akususi isixwayiso sokusebenzisana kwemithi, futhi ilebula yamanje yomkhiqizo onikwa ngomthambo inesixwayiso esisebhokisini ngalolu daba. Ngokwehlukana, ukuntuleka kwe-glucose-6-phosphate dehydrogenase kuyisimo esenqabela ukusetshenziswa ngoba i-methylene blue ingabangela ukubhidlika kwamangqamuzana egazi abomvu, futhi isivivinyo sesimanje asizifakanga iziguli ezinaleso simo. Noma ubani ohlanganisa le mithi udinga ukuqondiswa udokotela; lokhu kungukusebenza kwemithi okunezindlela zangempela zokubangela umonakalo, hhayi ukusebenzisana okungenabungozi kwezithasiselo.
Lokhu kuwushiya kuphi umbuzo
Ucwaningo lwe-methylene blue ekuphazamisekeni kwe-bipolar luncane, ludala, futhi lunikeza izinkomba, lwengezwe ucwaningo olulodwa lwesimanje lokuqala oluhloniphekile. Isifinyezo esithembekile: i-methylene blue engezwa ekwelashweni cishe ngo-195 kuya ku-300 mg nsuku zonke yanciphisa ngokuphindaphindiwe izimpawu zokucindezeleka nezisele kumasampula amancane, yabonisa uphawu lomphumela ekukhathazekeni kanye, ayibonisanga inzuzo emakhonweni okuqonda, ayibonisanga umphumela wokunciphisa i-mania, futhi ayibonisanga uphawu lokushintshela ku-mania olwalungabonwa yilezi zinani zabahlanganyeli. Azikenziwa izivivinyo ezinkulu ezinokulawulwa nge-placebo yangempela, amaqembu anokucindezeleka kwe-bipolar esigabeni esibukhali, ukuqapha ukushintshela ku-mania okunqunywe kusengaphambili, kanye nezinqubo ezanele zokufihla ukwelashwa. Kuze kube ziyenziwa, i-methylene blue isalokhu iyindlela yokwelashwa okwengeziwe esacwaningwa kulesi simo, eheha ngokwanele ukuba icwaningwe kabanzi kodwa enobufakazi obuncane kakhulu ukuba isekele iziphetho.